Knockdown of hsa_circ_0134111 alleviates the symptom of osteoarthritis via sponging microRNA-224-5p

Zhang, Lecheng; Sui, Cong; Zhang, Yuelei; Wang, Gang; Yin, Zongsheng

doi:10.1080/15384101.2021.1919838

Cited by 19 publications

(11 citation statements)

References 32 publications

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“…This search identified miR-1238, miR-1248, miR-1307, miR-224-5p, and miR-578 as candidate targets. Among these miRNAs, miR-224-5p was reported to be closely related to the pathogenesis of OA [ 8 , 19 , 20 ]. Therefore, we focused on exploring the relationship between hsa_circ_0134111 and miR-224-5p.…”

Section: Resultsmentioning

confidence: 99%

“…Zhou et al suggested that circRNA 33186 is involved in the development of OA through sponging miR-127-5pECM to influence catabolism, proliferation, and apoptosis [ 6 ]. In turn, Wang et al suggested a diagnostic value for hsa_circ_0032131_CBC1 in OA pathogenesis and identified hsa_circ_0134111 as a significantly upregulated ncRNA in OA tissues [ 7 , 8 ]. In addition, Wu et al reported that the importance of hsa_circ_0134111 in OA by regulating miR-515-5p [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction

Yong-bao

Zhang

2021

Aging

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Mechanical, metabolic, inflammatory, and immune factors contribute to the development of osteoarthritis (OA), a joint disease characterized by cartilage destruction. The circular RNA (circRNA) hsa_circ_0134111 is upregulated in the cartilage of OA patients; however, its potential role in OA pathogenesis and progression remains unexplored. In this study, the effects of hsa_circ_0134111 knockdown were evaluated in primary human chondrocytes treated with IL-1β to simulate OA, as well as in a rat model of OA. Hsa_circ_0134111 expression was upregulated in IL-1β-stimulated chondrocytes. CCK-8 and flow cytometry assays showed that hsa_circ_0134111 knockdown reversed IL-1β-induced cell decline by inhibiting apoptosis. Following prediction analysis of circRNA and miRNA targets, dual-luciferase reporter and silencing/overexpression assays suggested that a regulatory network composed of hsa_circ_0134111, miR-224-5p, and CCL1 modulates IL-1β-mediated OA-like effects in chondrocytes. Accordingly, CCL1 overexpression abrogated the prosurvival effects of hsa_circ_0134111 knockdown in vitro . Moreover, hsa_circ_0134111 silencing in vivo alleviated cartilage destruction in an OA rat model, decreased IL-6 and TNF-α levels in synovial fluid, and downregulated CCL1 expression in the affected joints. These results suggest that hsa_circ_0134111 contributes to OA development by binding to miR-224-5p, thereby releasing the inhibition that miR-224-5p exerts over CCL1.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction

Yong-bao

Zhang

2021

Aging

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“…Wu et al [ 41 ] demonstrated that knockdown of circ_0134111 relieved IL-1β-induced inflammation, apoptosis, and ECM degradation through the miR-515-5p/SOCS1 axis in the human chondrocytes. Zhang et al [ 42 ] showed that knockdown of circ_0134111 alleviated osteoarthritis symptoms through sponging miR-224-5p. Liu et al [ 34 ] also found that circ_0134111 induced osteoarthritis development through modulating the miR-224-5p/CCL1 axis.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0134111 promotes intervertebral disc degeneration via sponging miR-578

et al. 2022

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Intervertebral disc degeneration (IDD) is a chronic degenerative and age-dependent process characterized by aberrant apoptosis, proliferation, synthesis, and catabolism of the extracellular matrix of the nucleus pulposus (NP) cells. Recently, studies showed that circular RNAs play important roles in the development of many diseases. However, the role of circRNAs in IDD development remains unknown. We showed that circ_0134111 level was overexpressed in IDD tissue samples as compar-ed to control tissues. The upregulation of circ_0134111 was more drastic in the moderate and severe IDD cases than in those with mild IDD. In addition, we showed that interleukin-1β and tumor necrosis factor-α exposure significantly enhanced circ_0134111 expression in NP cells. Furthermore, ectopic expression of circ_0134111 induced proliferation, pro-inflammatory cytokine secretion, and ECM degradation in the NP cells. We also showed that circ_0134111 directly interacted with microRNA (miR)-578 in NP cells where elevated expression of circ_0134111 enhanced the ADAMTS-5 and MMP-9 expression. Moreover, miR-578 expression was significantly decreased in IDD patients and the miR-578 expression was negatively correlated with circ_0134111 expression in the IDD samples. Interleukin-1β and tumor necrosis factor-α exposure significantly decreased miR-578 levels in NP cells, in which ectopic miR-578 expression inhibited cell growth, pro-inflammatory cytokine expression, and ECM degradation. Finally, we showed that circ_0134111 overexpression induced the IDD-related phenotypic changes through inhibiting miR-578. These data suggested that circ_0134111 could promote the progression of IDD through enhancing aberrant NP cell growth, inflammation, and ECM degradation partly via regulating miR-578.

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“…JAK/STAT is associated with the expression miR-224 in osteogenic differentiation. Conversely, miR-224-5p can also promote cartilage degradation and aggravate OA by activating JAK2/STAT pathway ( 128 , 129 ). miR-149-5p has been shown to be an early biomarker of OA, and JAK inhibitors exhibit therapeutic effects against OA through inhibiting the expression of miR-149-5p ( 130 ).…”

Section: The Involvement Of Microrna In the Regulation Of Jak/stat Pa...mentioning

confidence: 99%

“…MiR-149/JAK1/IL-6/TNF-α axis plays a key role in maintaining joint tissue homeostasis. Specifically, miR-224-5p activates JAK2/STAT pathway by targeting CCL2, thereby promoting cartilage degradation and exacerbating symptoms in OA patients ( 129 ). In contrast, tofacitinib (a JAK inhibitor) affects miR-149 expression in C28/I2 cells and inhibited JAK/IL-6/TNF-α pathway, reducing arthritis scores and bone degradation in mice ( 130 ).…”

Section: The Involvement Of Microrna In the Regulation Of Jak/stat Pa...mentioning

confidence: 99%

The potential roles of JAK/STAT signaling in the progression of osteoarthritis

et al. 2022

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Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

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Knockdown of hsa_circ_0134111 alleviates the symptom of osteoarthritis via sponging microRNA-224-5p

Cited by 19 publications

References 32 publications

Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction

Hsa_circ_0134111 promotes osteoarthritis progression by regulating miR-224-5p/CCL1 interaction

Hsa_circ_0134111 promotes intervertebral disc degeneration via sponging miR-578

The potential roles of JAK/STAT signaling in the progression of osteoarthritis

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